1. Field of the Invention
The present invention relates to a process for oxidizing alkyne alcohols (alkynols) to alkynecarboxylic acids (alkynoic acids).
2. The Prior Art
Alkynoic acids are important synthetic building blocks. Of particular importance are propiolic acid and acetylene-dicarboxylic acid which are used to build rings in cycloadditions, in particular Diels-Alder reactions and 1,3-dipolar cycloadditions, and in nucleophilic addition reactions (overview in Ullmann's Encyclopedia, 6th Edition, 2001 electronic release; “Carboxylic acids, aliphatic 5.2”).
The oxidation of alkynols to alkynoic acids has been described in the prior art (overviews in Ullmann's Encyclopedia, 6th Edition, 2001 electronic release; “Carboxylic acids, aliphatic 5.2”; Houben-Weyl volume V/2a, 4th edition 1977, “Alkynes”)
For example, propiolic acid is obtained by anodic oxidation of propargyl alcohol (Wolf, Chem. Ber. 1954, 87, 668). Acetylenedicarboxylic acid is likewise obtained by anodic oxidation of 2-butyne-1,4-diol. However, the electrochemical process has the disadvantage of the use of lead dioxide anodes which leads to the contamination of the electrolytes with lead ions and can generally only be used in production at high capital cost. In addition, the decarboxylation of the product proceeding as a side reaction leads to technically undesired formation of large amounts of CO2 and acetylene which have to be disposed of. Also, the yields in the case of propiolic acid are relatively low (less than 50%).
The analogous anodic oxidation on nickel oxide anodes (Kaulen and Schäfer, Tetrahedron 1982, 38, 3299) requires low current densities and very large electrode surface areas, which leads to a further increase in the capital costs. In addition, the activated nickel surface is passivated during the electrolysis and frequently has to be regenerated which leads to an increase in the process costs.
Propiolic acid can also be obtained by oxidation of propargyl alcohol with Cr(VI) oxide in sulfuric acid. Good yields can be achieved, but large amounts of toxic and environmentally hazardous heavy metal salts have to be disposed of. The analogous reaction of 2-butyne-1,4-diol leads to only a 23% yield of acetylenedicarboxylic acid (Heilbron, Jones and Sondheimer, J. Chem. Soc. 1949, 606).
A known nonoxidative preparation process of propiolic acid and acetylenedicarboxylic acid is the reaction of metal acetylides with CO2. However, this requires the use of expensive metal bases and, owing to the use of acetylene, is technically not without risk. The yields of this process in the case of propiolic acid are likewise only 50%.
In a further process for preparing acetylenedicarboxylic acid, fumaric acid is initially converted with bromine to meso-dibromosuccinic acid, which is then isolated and dehalogenated in a further stage. This two-stage process is time-consuming and laborious (T. W. Abbott et al., Org. Synth. Coll. Vol. II, 1943, 10).
The prior art discloses general oxidation processes of alcohols to carboxylic acids with the aid of nitroxyl compounds as catalysts, in particular with the aid of nitroxyls such as TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) and its derivatives (overview in A. E. J. de Nooy, A. C. Besemer and H. V. Bekkum, Synthesis 1996, 1153).
TEMPO-catalyzed oxidations of alcohols to carboxylic acids are carried out in biphasic systems, for example methylene chloride/water and also in the presence of phase transfer catalysts (G. Grigoropoulou et al., Chem. Commun. 2001, 547–548, P. L. Anelli, C. Biffi, F. Montanari and S. Quici, J. Org. Chem. 1987, 52, 2559). The stoichiometric oxidant used is predominantly bleaching liquor (hypochlorite solution).
In the customary performance of these syntheses in biphasic systems, the oxidant dissolved in the aqueous phase, which is adjusted to a pH range of 8.5–9, is added in a batch process to an initially charged organic phase which comprises the alcohol to be oxidized, the phase transfer catalyst and the nitroxyl compound.
The prior art discloses that such oxidation processes using bleaching liquor and nitroxyl compounds are generally to be considered as unsuitable for the oxidation of unsaturated alcohols (on this subject, compare in particular P. L. Anelli, C. Biffi, F. Montanari and S. Quici, J. Org. Chem. 1987, 52, 2559; P. L. Anelli, F. Montanari and S. Quici, Org. Synth., 1990, 69, 212).
For instance, the reaction of an alkyne alcohol without terminal alkyne group (3-phenylpropynol) with bleaching liquor and TEMPO by the process disclosed in the prior art affords only unacceptable low yields of from 5 to a maximum of 20 mol % of the alkynoic acid (M. Zhao et al., J. Org. Chem. 1999, 64, 2564; WO 99/52849).
The oxidation of alkynols with terminal alkyne group with bleaching liquor and TEMPO at pH>7 has hitherto not been described.
A possible cause is the sensitivity disclosed by the literature of terminal alkyne groups toward bleaching liquor. The CH groups of terminal alkynes are easily converted, for example, to chloroalkynes by bleaching liquor, which are particularly labile in alkaline media and tend to decompose (Straus et al., Ber. Dtsch. Chem. Ges. 1930, 1868). This is especially true in the case of alkaline reaction conditions, since the acidic terminal acetylene unit is particularly readily halogenated. The resulting 3-halopropiolates are additionally compounds which decompose easily and have a tendency toward explosion.